Hypoxia has been identified as an important stimulus for gene expression during embryogenesis and in various pathological situations. Its influence under physiological conditions, however, has only been studied occasionally. We therefore investigated the effect of intermittent high altitude hypoxia on the mRNA expression of different cytokines and protooncogenes, but also of other genes described to be regulated by hypoxia, in the left ventricle (LV), the right ventricle (RV), atria and the lung of adult rats after simulation of hypoxia in a barochamber (5000 m, 4 hours to 10 days). Heme oxygenase-1 as well as transforming growth factor-β1 showed an increased expression in all regions of the heart and the lung at different periods of hypoxia. For lactate dehydrogenase-A, we found a significant up-regulation in the RV and the lung, for lactate dehydrogenase-B up-regulation in the RV, but down-regulation in the LV and the atria. Vascular endothelial growth factor was up-regulated in the RV, the LV and the lung, but down-regulated in the atria. Its receptor Flk-1 mRNA was significantly increased in the atria and RV only. Expression of c-fos was found in the LV and RV only after 4 hours of hypoxia. The level of c-jun was significantly increased in the LV but decreased in the atria. Our data clearly demonstrate that intermittent hypoxia is a modulator of gene expression under physiological conditions. It differently regulates the expression of distinct genes not only in individual organs but even within one organ, i.e. in the heart., E. Deindl, F. Kolář, E. Neubauer, S Vogel, W. Schaper, B. Ošťádal., and Obsahuje bibliografii
An increase in brain superoxide dismutase activity was found in rats exposed to high altitude hypoxia (7000 m, 30 min daily for five days) and ascorbic acid treatment (1 mg.g'1 daily s.c.) while no significant change was observed after high altitude hypoxia or ascorbic acid alone.
Quinidine-like immunoreactivity (Abbott TDx Quinidine fluorescence polarization immunoassay) was measured in blood serum of control rats and rats exposed to hypoxia in a hypobaric chamber (7 500 m for one hour). The mean "quinidine" levels (mean±S.D.) were 0.159±0.058 and 0.260±0.110 («mol quinidinq/1 serum), respectively (p<0.01).
Pregnant rats were exposed to intermittent hypobaric hypoxia (at a simulated altitude of 7000 m or 5000 m) and the excitability of cortical neurons of their pups was tested. Stimulation of the sensorimotor cortex of rats prenatally exposed to hypoxia shortened the duration of cortical afterdischarges in 12-day-old rats, but did not change the excitability in 25-day-old animals. Shortening of the first afterdischarge in 35-day-old rats but the prolongation of the first afterdischarge in adult rats (as compared to the duration of cortical afterdischarges in rats not exposed to prenatal hypoxia) were registered. The possible mechanisms of different excitability of cortical neurons in rats prenatally exposed to hypobaric hypoxia are discussed., D. Marešová, I. Valkounová, K. Jandová, J. Bortelová, S. Trojan., and Obsahuje bibliografii
Estrogen replacement therapy could play a role in the reduction of injury associated with cerebral ischemia in vivo, which could be, at least partially, a consequence of estrogen influence of glutamate buffering by astrocytes during hypoxia/ischemia. Estrogen exerts biological effects through interaction with its two receptors: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), which are both expressed in astrocytes. This study explored effects of hypoxia and glucose deprivation (HGD), alone or followed by 1 h recovery, on ERα and ERβ expression in primary rat astrocyte cultures following 1 h exposure to: a) 5 % CO2 in air (control group-CG); b) 2 % O2/5 % CO2 in N2 with glucose deprivation (HGD group-HGDG); or c) the HGDG protocol followed by 1 h CG protocol (recovery group-RG). ER α mRNA expression decreased in HGDG. At the protein level, full-length ER α (67 kDa) and three ER α -immunoreactive protein bands (63, 60 and 52 kDa) were detected. A significant decrease in the 52 kDa band was seen in HGDG, wh ile a significant decrease in expression of the full length ERα was seen in the RG. ERβ mRNA and protein expression (a 54 kDa single band) did not change. The observed decrease in ER α protein may limit estrogen-mediated signalling in astrocytes during hypoxia and recovery., M. D. Al-Bader, S. A. Malatiali, Z. B. Redzic., and Obsahuje bibliografii a bibliografické odkazy
We investigated the influence of oxygenation of in vitro lung preparation on the pulmonary vascular reactivity. Small pulmonary vessels isolated from adult male Wistar rats exposed for 4 days to hypoxia (FiO2 = 0.1, group CH) were compared with those of normoxic controls (group N). The bath in the chamber of small vessel myograph was saturated with gas mixture containing either 21 % or 95 % of O2 with 5 % CO2 and we measured the reactions of vessels to acute hypoxic challenge with 0 % O2 or to PGF2α. We did not observe any difference of the contractile responses between both groups when the normoxic conditions were set in the bath. When the bath oxygenation was increased to 95 % O2, the contractions induced by hypoxic challenge and PGF2α decreased in chronically hypoxic rats and did not change in normoxic controls. We hypothesize that reduced reactivity of vessels from hypoxic rats in hyperoxia results from the effect of chronic hypoxia on Ca2+ signaling in the vascular smooth muscle, which is modulated by increased free radical production during the exposure to chronic hypoxia and further hyperoxia., M. Žaloudíková, M. Vízek, J. Herget., and Obsahuje seznam literatury
In experiments on 2-day-old rats (Wistar strain, our own breed), we studied the effect of altitude hypoxia (9000 m, 60 min) on the proportion of individual fatty acids in the brain (the cortex + the diencephalon + the cranial third of the mesencephalon). We found that hypoxia significantly altered the proportion of the various fatty acids, with a significant increase in the proportion of group n-3 polyenoic fatty acids at the expense of saturated and monoenoic acids. The results fully confirm the conception that one of the most important mechanisms responsible for the high resistance of new born mammals to oxygen deficiency is the ability of immature nervous tissue to activate, in particular, elongation (the elongation of fatty acids) and/or lipogenetic processes.
Gastric cancer is characterized by the presence of high invasion ability, hypoxia and chemoresistance. Previous studies reported that liver X receptor α (LXRα) was involved in epithelial-mesenchymal transition (EMT) of gastric cancer cells. However, hypoxia-mediated EMT and the role of LXRα in gastric cancer remained elusive. In this study, we demonstrated that LXRa mRNA and protein levels were up-regulated by hypoxia treatment and LXRα played an important role in HIF-1 dimer induced-EMT. The putative HIF-1α binding site was identified in the LXRa promoter. Expression of LXRα and HIF-1α was significantly up-regulated in gastric cancer tissues compared to that in normal tissues. More importantly, we noticed that the expression of LXRα and HIF-1α was significantly correlated. Taken together, these data suggested that LXRα is regulated by the activity and accumulation of HIF-1α and contributes to EMT of gastric cancer cells. This suggests that targeting LXRα might be a potential approach for improving survival of gastric cancer patients.
a1_Vascular repair in response to injury or stress (often referred to as remodeling) is a common complication of many cardiovascular abnormalities including pulmonary hypertension, systemic hypertension, atherosclerosis, vein graft remodeling and restenosis following balloon dilatation of the coronary artery. It is not surprising that repair and remodeling occurs frequently in the vasculature in that exposure of blood vessels to either excessive hemodynamic stress (e.g. hypertension), noxious blood borne agents (e.g. atherogenic lipids), locally released cytokines, or unusual environmental conditions (e.g. hypoxia), requires readily available mechanisms to counteract these adverse stimuli and to preserve structure and function of the vessel wall. The responses, which were presumably evolutionarily developed to repair an injured tissue, often escape self-limiting control and can result, in the case of blood vessels, in lumen narrowing and obstruction to blood flow. Each cell type (i. e. endothelial cells, smooth muscle cells, and fibroblasts) in the vascular wall plays a specific role in the response to injury. However, while the roles of the endothelial cells and smooth muscle cells (SMC) in vascular remodeling have been extensively studied, relatively little attention has been given to the adventitial fibroblasts. Perhaps this is because the fibroblast is a relatively ill-defined cell which, at least compared to the SMC, exhibits few specific cellular markers. Importantly though, it has been well demonstrated that fibroblasts possess the capacity to express several functions such as migration, rapid proliferation, synthesis of connective tissue components, contraction and cytokine production in response to activation or stimulation., a2_The myriad of responses exhibited by the fibroblasts, especially in response to stimulation, suggest that these cells could play a pivotal role in the repair of injury. This fact has been well documented in the setting of wound healing where a hypoxic environment has been demonstrated to be critical in the cellular responses. As such it is not surprising that fibroblasts may play an important role in the vascular response to hypoxia and/or injury. This paper is intended to provide a brief review of the changes that occur in the adventitial fibroblasts in response to vascular stress (especially hypoxia) and the role the activated fibroblasts might play in hypoxia-mediated pulmonary vascular disease., K. R. Stenmark, D. Bouchey, R. Nemonoff, E. C. Dempsey, M. Das., and Obsahuje bibliografii